Synthesis And Properties Of Unsaturated Polyphosphoester Used As A Potential Injectable Bone Repair Material

Injectable bone repair biomaterials have been developed because they can fill irregularly shaped defects and may allow bone augmentation, both with minimal surgical intervention. These injectable biomaterials could crosslink in situ to form a three dimensional network with suitable properties. Polyphosphoesters are analogs of nucleic and teichoic acids with excellent biodegradability and biocompatibility. The phosphoester bond in the polyphosphoester backbone can be cleaved by water and possibly enzymatic digestion under physiological conditions. The flexible P-O-C bonds in the backbone make polyphosphoesters commonly with low glass transition temperature and show poor mechanical strength in physiological temperature. In this work, in order to improve mechanical property of polyphosphoesters and meet the demand of bone repair materials, a novel crosslinkable polyphosphoester based on bis(1,2-propylene glycol) fumarate(BPGF) and ethyl dichlorophosphate was designed which contained unsaturated double bonds in backbone.The monomer BPGF was synthesized by a new method without any solvent. Purity and yield of BPGF were both rose remarkably comparing with the reported method. Three possible bonding models in polyphosphoester chain resulting from three isomers of bis(1,2-propylene glycol) fumarate was confirmed by NMR and GC-MS spectra. Unsaturated polyphosphoester(UPPE) can be crosslinked through the double bonds along with its backbone. Vinyl monomer, such as N-vinyl pyrrolidone(NVP) and 2-hydroxyethyl methacrylate can be used as crosslink agent. Polymer network formed by UPPE and NVP through in situ crosslinking reaction initiated by BPO-DMT system. For all formulations, the maximum crosslinking temperature was between 46.49 to 93.07℃which was lower than that of 97℃for poly(methyl methacrylate) bone cement. The setting time was between 1.7 to 10.3 minutes, and strongly affected by BPO/UPPE ratio. Maximum compressive strength and compressive modulus values of crosslinked UPPE/β-tricalcium phosphate composite were 94.36±6.96 MP and 2096.93±92.86 MPa, which were higher than those of human trabecular bone.In order to control polymerization exotherm and facilitate the operating conditions, the crosslinking reaction of UPPE and NVP initiated by UV light has also been investigated. Results show that the gel content of curing product was remarkably improved by addition of photoinitiators The gel content of crosslinked network obtained from UPPE with Mw=4040 g/mol is lower than that of with higher molecular weight when the irradiation time was less than 2 minutes, but an opposite results would obtained by extending irradiation time. The surface layer of sample absorbed the UV light and decreased the photocrosslink reaction rate of the deep layer.Weight and mechanical strength of all formulations were decreased rapidly within the first two days during degradation experiment. Following the first stage, very slowly decreased in weight and mechanical strength was observed during the remaining degradation time. Increasing UPPE molecular weight andβ-tricalcium phosphate incorporation resulted in an increase in both compressive strength and compressive modulus, and a decrease in weight loss.In order to improve the osteoconductivity, a simple process was developed to deposit a mineral layer on the surface of crosslinked UPPE. It was found that mineral fibrous grown upwards from the surface of crosslinked UPPE. Composition of fibre was calcium deficient carbonated apatite with low crystallinity. SEM micrograph indicated that the fibre had a hollow tubing structure and the tube wall was a flakelike assembly. The growth was at the tip of the fibre at a rate about 0.5mm/min and reached several centimeters in length after 2 hours.Crosslinked UPPE/β-tricalcium phosphate composites exhibited good biocompatibility and no deleterious long-term inflammatory response when be implanted subcutaneously in rats.